Methods and systems for analyzing t-wave alternans

ABSTRACT

Embodiments of the present invention relate to implantable systems, and methods for use therein, that can detect T-wave alternans and analyze the detected alternans to provide information regarding cardiac instabilities and predict impending arrhythmias.

PRIORITY CLAIM AND CROSS REFERENCE TO RELATED APPLICATIONS

This application is a Divisional application of U.S. patent applicationSer. No. 13/563,522 (Attorney Docket No. A08P3011-US2), filed Jul. 31,2012, entitled “METHODS AND SYSTEMS FOR ANALYZING T-WAVE ALTERNANS,”which is a Continuation of U.S. patent application Ser. No. 12/456,628(Attorney Docket No. A08P3011-US1), filed Jun. 18, 2009, entitled“METHODS AND SYSTEMS FOR ANALYZING T-WAVE ALTERNANS,” now U.S. Pat. No.8,255,043 which claims the benefit of U.S. Provisional PatentApplication No. 61/073,666 (Attorney Docket No. A08P3011) entitled“METHODS AND SYSTEMS FOR ANALYZING T-WAVE ALTERNANS” filed Jun. 18,2008. Each patent application identified above is incorporated herein byreference in its entirety to provide continuity of disclosure.

This application is also a Continuation-In-Part application of andclaims priority and other benefits from U.S. patent application Ser. No.12/340,352 (Attorney Docket No. A08P3020), filed Dec. 19, 2008, entitled“Monitoring Variation Patterns in Physiological Parameters Associatedwith Myocardial Instability,” now U.S. Pat. No. 8,457,727, thespecification of which is expressly incorporated herein by reference inits entirety to provide continuity of disclosure.

Cross Reference to Related Applications

The present invention relates to the following commonly assignedapplications, each of which is incorporated herein by reference: U.S.patent application Ser. No. 10/186,069, entitled “Implantable CardiacDevice Having a System for Detecting T-Wave Alternan Patterns andMethod,” filed Jun. 28, 2002 (Attorney Docket No. A02P1050), grantedApr. 11, 2006 as U.S. Pat. No. 7,027,867; U.S. patent application Ser.No. 10/868,240, entitled “Implantable Cardiac Device Providing RapidPacing T-wave Alternan Pattern Detection and Method,” filed Jun. 14,2004 (Attorney Docket No. A02P1050US01), granted Jul. 17, 2007 as U.S.Pat. No. 7,027,867; U.S. patent application Ser. No. 11/229,411,entitled “Methods and Systems for Detecting the Presence of T-WaveAlternans,” filed Sep. 16, 2005 (Attorney Docket No. A05P3017-US1); andU.S. patent application Ser. No. 11/229,410, entitled “Methods andSystems for Detecting the Presence of T-Wave Alternans,” filed Sep. 16,2005 (Attorney Docket No. A05P3017-US3).

FIELD OF THE INVENTION

The present invention generally relates to an implantable cardiac devicethat delivers electrical therapy to a patient's heart. The presentinvention more particularly relates to such a device capable ofdetecting T-wave alternan patterns.

BACKGROUND

Electrical alternans relate to the differences in electrical potentialat corresponding points between alternate heartbeats. T-wave alternansor alternation is a regular or beat-to-beat variation of the ST-segmentor T-wave of an electrocardiogram (ECG) which repeats itself every twobeats and has been linked to underlying cardiac instability. Typically,by enumerating all consecutive heart beats of a patient, beats with anodd number are referred to as “odd beats” and beats with an even numberare referred to as “even beats.” A patient's odd and even heartbeats mayexhibit different electrical properties of diagnostic significance whichcan be detected by an ECG.

The presence of these electrical alternans is significant becausepatients at increased risk for ventricular arrhythmia's commonly exhibitalternans in the ST-segment and the T-wave of their ECG. Clinicians maytherefore use these electrical alternans as a noninvasive marker ofvulnerability to ventricular tachyarrhythmias. The term T-wave alternans(TWA) is used broadly to denote electrical alternans such as these. Itshould be understood that the term encompasses both the alternans of theT-wave segment and the ST-segment of an ECG.

T-wave alternans (TWA) has been demonstrated in many studies as a strongpredictor of mortality, independent of left ventricular ejectionfraction (LVEF). More specifically, it has become well known that T-wavealternans has predictive value for arrhythmic events such astachyarrhythmias. Additionally, T-wave alternans has been determined tobe an indicator of various forms of disordered ventricularrepolarization, including disorders found in patients withcardiomyopathy, mild to moderate heart failure, and congestive heartfailure.

T-wave alternans (TWA) may be caused by changes in ion exchange duringrepolarization. If there is a change in the repolarization mechanism onone beat, the heart attempts to readjust on the following beat, This ismanifested as an alternating change in the action potential. In thesurface ECG this is seen primarily as an amplitude change. For animplanted medical device such as a cardiac pacemaker, the intracardiacelectrogram (IEGM) also shows a change in timing. Thus, the term T-waveas used herein may refer to a portion of the ventricular QRS-T-wavecomplex that includes the T-wave and the QRS-T segment. The alternatingfeature of TWA can be detected by examination, for example, of the QTinterval, T-wave width, T-wave amplitude and morphology, etc. Whateverthe designated portion of the intracardiac electrogram, T-wave alternansrefers to an alternating pattern of the wave that can be designated“A-B-A-B-A . . . ” where A represents every other cycle and B representsevery other alternate cycle. As discussed in the literature, when suchan alternating pattern appears, the different rates or forms ofrepolarization of the ventricular cells are statistically associatedwith a variety abnormal cardiac conditions. Further, the alternatingrepolarization pattern can lead to increased instability and consequentcardiac arrhythmias. Thus, the presence of T-wave alternans isrecognized as an indicator of risk for ventricular arrhythmia and evensudden cardiac death (SCD).

In the past, detection of T-wave alternan patterns has been performedusing surface ECGs. Implementation of such detection has included themeasurement, on a beat-to-beat basis, of the micro-volt level changes inthe T-wave amplitude from the surface ECG. Then, the long record of timeseries of T-wave amplitude change is transformed into the frequencydomain by Fourier series transformation (FFT). A prominent peak in theFFT at 0.5 Hz would verify the existence of a T-wave alternan pattern.

Unfortunately, the above detection method requires the use of medicalequipment that must be operated by medical personnel in a medicalfacility such as a physician's office. The detection requires long termrecording of surface ECGs and off-line analysis with robust computationequipment. As a result, T-wave alternan pattern monitoring has beeninconvenient and cumbersome. As a result, it is difficult to providecontinuous and regular T-wave alternan pattern monitoring.

Many patients who would benefit from T-wave alternan pattern monitoringhave an implanted cardiac device such as an implantable defibrillator ora combined defibrillator pacemaker. It would thus be highly desirable ifsuch an implanted device could monitor for T-wave alternan patterns.However, the prior art detection method does not lend itself for suchapplication due to, for example, the required long term monitoring,surface ECG, and robust computational requirements for Fourier seriestransformation.

Several studies have demonstrated that the beat by beat alterations (inECG and EGM recordings) before the onset of VT/VF are significantlydifferent to that in control recordings. These findings support thefeasibility of early prediction of arrhythmia occurrence. However, therelationship between the degree of beat by beat alterations prior toVT/VF and the complexity of VT/VF has not been known. Since beat by beatalterations indicate the dynamic instability within the heart, it playsan important role in the maintenance of VT/VF. Therefore, it is usefulto predict the complexity of VT/VF by the degree of alterations beforethe onset of this VT/VF.

T waves in ECGs and IEGMs are a manifestation of the dispersion ofrepolarization within the heart. Due to the adaptability inrepolarization phase, both T wave morphology and the duration between Twave to R wave are different when heart rate changes. Severalmathematical formulas have been established and used in ECG dataanalysis for compensating the effects of heart rate on Q-T interval.However, these equations cannot be directly applied to IEGM signalanalysis because of the morphological difference between the two signalscaused by recording location as well as the fact that IEGM signals areattenuated by the internal filter in the device.

Recent studies have demonstrated that T wave alternans significantlyincreased prior to the onset of ventricular arrhythmias in EGMrecording. Hence, it might be possible to predict the onset oftachyarrhythmias by continuous T wave alternans monitoring. In order toaccurately analyze T wave at various heart rate (including some cases ofsupraventricular arrhythmias), the device needs to know when the T wavestarts and ends.

Despite intensive research, occurrence of ventricular tachycardia (VT)and ventricular fibrillation (VF) remain highly unpredictable. Prematureventricular contraction (PVC) is very common in patients with structuraland functional heart diseases. A recent study in MADIT II patients withICDs revealed that 77% of the stored VFs were initiated by single PVC.This finding suggests that PVCs play an important role in arrhythmia (inparticular, VF) initiation.

On the other hand, the probability that PVCs will induce VT/VF isextremely low. For example, a patient has just one PVC per minute willhave about half million PVCs per year, but VT/VF episodes in thesepatients occur over months to years, not minutes. Therefore, it islikely that majority of the PVCs do not happen at a critical vulnerableperiod except a few of them.

In order for an implanted cardiac device to provide T-wave alternanpattern monitoring, there is a need for a new and different approach.The present invention addresses that need.

BRIEF SUMMARY OF THE INVENTION

In accordance with one embodiment of the invention an approach toprospectively predict the complexity of arrhythmias based on beat bybeat alterations before the actual arrhythmia onset is provided. Thismethod provides an early prediction of an arrhythmia and allows foroptimizing antiarrhythmia therapy. In this embodiment, the method isused in implantable devices to predict the complexity of coming VT/VFbased on beat by beat alterations before the actual onset of VT/VF. Themethod extracts EGM features and tracks beat by beat alterations. Thesefeatures may include the amplitude, duration, slope, area under thecurve of QRS complex and T wave portion, as well as conduction velocity.Table 1. illustrates some features that can be extracted fromventricular IEGM. Based on the degree of alterations, the methodpredicts the complexity of VT/VF and selects optimal therapy. Forexample, reduce the number of ATP attempts when the method predicts highcomplexity.

In another embodiment of the invention, a heart rate dependent T wavecorrection which can be used in T wave alternans detection in EGMrecordings is disclosed. A general form of the equation is:

$\begin{matrix}{T = \frac{A}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{B} \right)^{k}}} & {{Eq}.\mspace{14mu} 1}\end{matrix}$

For example, the equation below identifies T wave accurately for heartrate ranging from 50 to 160 as provided in FIG. 3 where T wave start andend time from R wave for heart rate ranged from 50 to 160 bpm.

$\begin{matrix}{T_{start} = \frac{160}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{60} \right)^{0.5}}} & {{Eq}.\mspace{14mu} 2} \\{T_{end} = \frac{480}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{70} \right)^{0.7}}} & {{Eq}.\mspace{14mu} 3}\end{matrix}$

where T_(start) & T_(end) are the start and end time from the peak ofthe QRS.

In another embodiment, a method used in implantable devices to identifyvulnerability and risk of arrhythmias is disclosed. Once a PVC isdetected, several features will be calculated and saved in the device.These features include averaged heart rate before the PVC, prematurecoupling interval of the PVC, averaged T wave duration before the PVC,and morphological characteristics (amplitude, large negative peak, etc.)of the PVC. The implantable device will also register lethal PVCcharacteristics if VT/VF (both sustained and non-sustained) is triggeredby a PVC. The characteristics of newly detected PVCs will be compared toan existing template to determine the likelihood of arrhythmiainitiation. If the chance of arrhythmia initiation is high, a device mayrespond correspondingly to reduce the chance of arrhythmia initiationthrough pacing interruption and may start to prepare antiarrhythmiatherapy before an arrhythmia happens such as by charging high voltagecapacitors.

In another embodiment of the invention provides a time domain method topredict risks of spontaneous VT/VF by tracking beat to beat alterationsin extracted EGM features. As an example, Table 1 lists the extractedfeatures from a ventricular EGM recording. Beat to beat alterations inamplitude and pattern from some or all of these extracted features willbe fed into a mathematical model to predict risks of arrhythmias.

This invention further consists of a new method to monitor thetransition pattern of beat by beat variation of any electrical andmechanical characteristics. These characteristics include but are notlimited to intervals (R-R interval, Q-T interval, etc), EGM amplitudes(QRS amplitude, T wave amplitude, etc), and their analogies derived fromintracardiac impedance. For any single or combined characteristic, thebeat by beat variation will be calculated by subtracting the valueassociated with the current beat by the value associated with itsprevious beat.

In one embodiment, the transition pattern of beat to beat variations inIEGM will be calculated by the percentage of reversal point (PRP) withina certain time window based on Eq. 3. PRP value will be used as a riskindicator of arrhythmias.

$\begin{matrix}{{PRP} = \frac{{{number}\mspace{14mu} {of}\mspace{14mu} {reversal}\mspace{14mu} {point}\mspace{14mu} {within}\mspace{14mu} {the}\mspace{14mu} {window}} - 2}{\begin{matrix}{{total}\mspace{14mu} {number}\mspace{14mu} {of}{\mspace{11mu} \;}{beats}\mspace{14mu} {from}} \\{\; {{{the}\mspace{14mu} 1\; {st}\mspace{14mu} {to}\mspace{14mu} {the}\mspace{14mu} {last}\mspace{14mu} {reversal}\mspace{14mu} {point}} - 2}}\end{matrix}\mspace{11mu}}} & {{Eq}.\mspace{14mu} 3}\end{matrix}$

FIG. 4 shows two examples with A-B (panel A) and A-B-C (panel B)patterns and their corresponding PRP values. The PRP value can becontinuously calculated in a moving window and generate detection alarmwhen the value falls into each block (e.g. PRP 0.9˜1 for A-B pattern,PRP 0.62˜0.72 for A-B-C pattern). In one method, PRP itself can be usedto trigger an alarm of vulnerable period to arrhythmias; in anothermethod, PRP will be combined into a multiple factors determiningalgorithm to trigger an alarm of vulnerable period to arrhythmias.

The PRP calculation will be corrected when PVC happens within thecalculation window. In one approach, PRP calculation will ignore the PVCbeats and the beats prior and after each PVC beat; in another approach,the value associated with a PVC beat will be replaced by an averagedvalue from the non-PVC beats before PRP calculation.

In another embodiment, the continuous oscillation pattern monitoring canbe used as an indicator of patient health status and diseaseprogression. If the PRP values within a period (e.g. a month) shows asignificant trend of increasing, an alarm indicating heart diseaseprogression or remodeling will be triggered.

In still another embodiment of the invention, a method thatautomatically calculates T wave start and end time based on the heartrate computed from the previous beat is disclosed. This allows one totruncate a portion from the EGM signals at every heart beat and extractcritical features related to T wave instability and correspondinglypredicts the onset of ventricular tachyarrhythmias.

Examples of other T-wave metrics that can be measured (i.e., besidesT-wave amplitude) include T-wave width, T-wave slope, T-wave area,T-wave morphology, QT interval, and evoked QT interval.

This description is not intended to be a complete description of, orlimit the scope of, the invention. Other features, aspects, and objectsof the invention can be obtained from a review of the specification, thefigures, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified diagram illustrating an exemplary ICD inelectrical communication with a patient's heart by means of three leadssuitable for delivering multi-chamber stimulation and pacing therapy,and a fourth lead suitable for delivering vagal stimulation.

FIG. 2 is a functional block diagram of an exemplary IDD that canprovide cardioversion, defibrillation, and pacing stimulation in fourchambers of a heart, and detect the presence of T-wave alternans, inaccordance with an embodiment of the present invention.

FIG. 3 is a graph illustrating the relationship between the start andend of the T-wave from the R-wave as a function of heart rate.

FIG. 4 shows two examples of alternans patterns and their correspondingPRP values.

FIG. 5 shows the points that can be monitored in a sensed or stored EGM.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description of the present invention refers tothe accompanying drawings that illustrate exemplary embodimentsconsistent with this invention. Other embodiments are possible, andmodifications may be made to the embodiments within the spirit and scopeof the present invention. Therefore, the following detailed descriptionis not meant to limit the invention. Rather, the scope of the inventionis defined by the appended claims.

It would be apparent to one of skill in the art that the presentinvention, as described below, may be implemented in many differentembodiments of hardware, software, firmware, and/or the entitiesillustrated in the figures. Any actual software and/or hardwaredescribed herein is not limiting of the present invention. Thus, theoperation and behavior of the present invention will be described withthe understanding that modifications and variations of the embodimentsare possible, given the level of detail presented herein.

Exemplary ICD

Before describing the invention in detail, it is helpful to describe anexample environment in which the invention may be implemented. Thepresent invention is particularly useful in the environment of animplantable cardiac device that can monitor electrical activity of aheart and deliver appropriate electrical therapy, for example, pacingpulses, cardioverting and defibrillator pulses, and drug therapy, asrequired. Implantable cardiac devices include, for example, pacemakers,cardioverters, defibrillators, implantable cardioverter defibrillators,and the like. The term “implantable cardiac device” or simply “ICD” isused herein to refer to any implantable cardiac device. FIGS. 1 and 2illustrate such an environment in which embodiments of the presentinvention can be used.

Referring first to FIG. 1, an exemplary ICD 10 is shown in electricalcommunication with a patient's heart 12 by way of three leads, 20, 24and 30, suitable for delivering multi-chamber stimulation and pacingtherapy. To sense atrial cardiac signals and to provide right atrialchamber stimulation therapy, ICD 10 is coupled to implantable rightatrial lead 20 having at least an atrial tip electrode 22, whichtypically is implanted in the patient's right atrial appendage.

To sense left atrial and ventricular cardiac signals and to provideleft-chamber pacing therapy, ICD 10 is coupled to “coronary sinus” lead24 designed for placement in the “coronary sinus region” via thecoronary sinus for positioning a distal electrode adjacent to the leftventricle and/or additional electrode(s) adjacent to the left atrium. Asused herein, the phrase “coronary sinus region” refers to thevasculature of the left ventricle, including any portion of the coronarysinus, great cardiac vein, left marginal vein, left posteriorventricular vein, middle cardiac vein, and/or small cardiac vein or anyother cardiac vein accessible by the coronary sinus.

Accordingly, exemplary coronary sinus lead 24 is designed to receiveatrial and ventricular cardiac signals and to deliver left ventricularpacing therapy using at least a left ventricular tip electrode 26, leftatrial pacing therapy using at least a left atrial ring electrode 27,and shocking therapy using at least a left atrial coil electrode 28.

ICD 10 is also shown in electrical communication with the patient'sheart 12 by way of an implantable right ventricular lead 30 having, inthis embodiment, a right ventricular tip electrode 32, a rightventricular ring electrode 34, a right ventricular (RV) coil electrode36, and a superior vena cave (SVC) coil electrode 38. Typically, rightventricular lead 30 is transvenously inserted into heart 12 so as toplace the right ventricular tip electrode 32 in the right ventricularapex so that RV coil electrode 36 will be positioned in the rightventricle and SVC coil electrode 38 will be positioned in the SVC.Accordingly, right ventricular lead 30 is capable of receiving cardiacsignals and delivering stimulation in the form of pacing and shocktherapy to the right ventricle.

In FIG. 1, ICD 10 is also shown as being in electrical communicationwith the patient's heart 12 by way of a vagal stimulation lead 25,having, e.g., three vagal stimulation electrodes 31, 33, and 35 capableof delivering stimulation bursts to the patient's vagus nerve.Alternatively, vagal stimulation electrodes 31, 33, and 35 can bepositioned in the epicardial fat pad near the sinoatrial (SA) node.Based on the description herein, one skilled in the relevant art(s) willunderstand that the invention can be implemented by positioning vagalstimulation electrodes 31, 33, and 35 in alternate locations, such as inproximity to the cervical vagus, or implanted near or inside the SVC,the inferior vena cava (IVC), or the coronary sinus (CS), where they arealso capable of delivering stimulation bursts to the patient's vagusnerve.

FIG. 2 shows a simplified block diagram of ICD 10, which is capable oftreating both fast and slow arrhythmias with stimulation therapy,including cardioversion, defibrillation, and pacing stimulation. While aparticular multi-chamber device is shown, it is shown for illustrationpurposes only, and one of skill in the art could readily duplicate,eliminate or disable the appropriate circuitry in any desiredcombination to provide a device capable of treating the appropriatechamber(s) with the desired cardioversion, defibrillation and pacingstimulation.

A housing 40 of ICD 10, shown schematically in FIG. 2, is often referredto as the “can,” “case” or “case electrode” and may be programmablyselected to act as the return electrode for all “unipolar” modes.Housing 40 may further be used as a return electrode alone or incombination with one or more of coil electrodes, 28, 36, and 38 forshocking purposes. Housing 40 further includes a connector (not shown)having a plurality of terminals, 42, 44, 46, 48, 52, 54, 56, 58, 218,219 and 220 (shown schematically and, for convenience, the names of theelectrodes to which they are connected are shown next to the terminals).As such, to achieve right atrial sensing and pacing, the connectorincludes at least a right atrial tip terminal (AR TIP) 42 adapted forconnection to atrial tip electrode 22.

To achieve left chamber sensing, pacing and shocking, the connectorincludes at least a left ventricular tip terminal (VL TIP) 44, a leftatrial ring terminal (AL RING) 46, and a left atrial shocking terminal(AL COIL) 48, which are adapted for connection to left ventricular ringelectrode 26, left atrial tip electrode 27, and left atrial coilelectrode 28, respectively.

To support right chamber sensing, pacing, and shocking the connectoralso includes a right ventricular tip terminal (VR TIP) 52, a rightventricular ring terminal (VR RING) 54, a right ventricular shockingterminal (RV COIL) 56, and an SVC shocking terminal (SVC COIL) 58, whichare configured for connection to right ventricular tip electrode 32,right ventricular ring electrode 34, RV coil electrode 36, and SVC coilelectrode 38, respectively.

The connector is also shown as including vagal lead terminals (VAGALELECTRODES) 218, 219, and 220, which are configured for connection tovagal stimulation electrodes 31, 33, and 35, respectively, to supportthe delivery of vagal stimulation bursts.

At the core of ICD 10 is a programmable microcontroller 60, whichcontrols the various modes of stimulation therapy. As is well known inthe art, microcontroller 60 typically includes one or moremicroprocessor, or equivalent control circuitry, designed specificallyfor controlling the delivery of stimulation therapy and can furtherinclude RAM or ROM memory, logic and timing circuitry, state machinecircuitry, and I/O circuitry. Typically, microcontroller 60 includes theability to process or monitor input signals (data) as controlled by aprogram code stored in a designated block of memory. The details of thedesign of microcontroller 60 are not critical to the present invention.Rather, any suitable microcontroller 60 can be used to carry out thefunctions described herein. The use of microprocessor-based controlcircuits for performing timing and data analysis functions are wellknown in the art.

Representative types of control circuitry that may be used with theinvention include the microprocessor-based control system of U.S. Pat.No. 4,940,052 (Mann et. al.) and the state-machines of U.S. Pat. No.4,712,555 (Sholder) and U.S. Pat. No. 4,944,298 (Sholder). For a moredetailed description of the various timing intervals used within theICD's and their inter-relationship, see U.S. Pat. No. 4,788,980 (Mannet. al.). The '052, '555, '298 and '980 patents are incorporated hereinby reference.

As shown in FIG. 2, an atrial pulse generator 70 and a ventricular pulsegenerator 72 generate pacing stimulation pulses for delivery by rightatrial lead 20, right ventricular lead 30, and/or coronary sinus lead 24via an electrode configuration switch 74. It is understood that in orderto provide stimulation therapy in each of the four chambers of theheart, atrial and ventricular pulse generators 70 and 72 may includededicated, independent pulse generators, multiplexed pulse generators,or shared pulse generators. Pulse generators 70 and 72 are controlled bymicrocontroller 60 via appropriate control signals 71 and 78,respectively, to trigger or inhibit the stimulation pulses.

Also shown in FIG. 2, is a vagal pulse generator 214 that is controlledby vagal stimulation control 210 (within microcontroller 60) via acontrol signal 212, to trigger or inhibit the delivery of vagalstimulation pulses.

Microcontroller 60 further includes timing control circuitry 79, whichis used to control pacing parameters (e.g., the timing of stimulationpulses) as well as to keep track of the timing of refractory periods,PVARP intervals, noise detection windows, evoked response windows, alertintervals, marker channel timing, etc., which are well known in the art.Examples of pacing parameters include, but are not limited to,atrio-ventricular (AV) delay, interventricular (RV-LV) delay, atrialinterconduction (A-A) delay, ventricular interconduction (V-V) delay,and pacing rate.

Switch 74 includes a plurality of switches for connecting the desiredelectrodes to the appropriate I/O circuits, thereby providing completeelectrode programmability. Accordingly, switch 74, in response to acontrol signal 80 from microcontroller 60, determines the polarity ofthe stimulation pulses (e.g., unipolar, bipolar, combipolar, etc.) byselectively closing the appropriate combination of switches (not shown)as is known in the art.

Atrial sensing circuits 82 and ventricular sensing circuits 84 may alsobe selectively coupled to right atrial lead 20, coronary sinus lead 24,and right ventricular lead 30, through switch 74 for detecting thepresence of cardiac activity in each of the four chambers of the heart.Accordingly, the atrial (ATR. SENSE) and ventricular (VTR. SENSE)sensing circuits 82 and 84 may include dedicated sense amplifiers,multiplexed amplifiers, or shared amplifiers. Switch 74 determines the“sensing polarity” of the cardiac signal by selectively closing theappropriate switches, as is also known in the art. In this way, aclinician may program the sensing polarity independent of thestimulation polarity.

Each sensing circuit, 82 and 84, preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables ICD 10 to deal effectively with thedifficult problem of sensing the low amplitude signal characteristics ofatrial or ventricular fibrillation. Such sensing circuits, 82 and 84,can be used to determine cardiac performance values used in the presentinvention.

The outputs of atrial and ventricular sensing circuits 82 and 84 areconnected to microcontroller 60 which, in turn, are able to trigger orinhibit atrial and ventricular pulse generators, 70 and 72,respectively, in a demand fashion in response to the absence or presenceof cardiac activity, in the appropriate chambers of the heart. Sensingcircuits 82 and 84, in turn, receive control signals over signal lines86 and 88 from microcontroller 60 for purposes of measuring cardiacperformance at appropriate times, and for controlling the gain,threshold, polarization charge removal circuitry (not shown), and timingof any blocking circuitry (not shown) coupled to the inputs of sensingcircuits 82 and 86.

For arrhythmia detection, ICD 10 utilizes the atrial and ventricularsensing circuits 82 and 84 to sense cardiac signals to determine whethera rhythm is physiologic or pathologic. The timing intervals betweensensed events (e.g., P-waves, R-waves, and depolarization signalsassociated with fibrillation are then classified by microcontroller 60by comparing them to a predefined rate zone limit (i.e., bradycardia,normal, low rate VT, high rate VT, and fibrillation rate zones) andvarious other characteristics (e.g., sudden onset, stability,physiologic sensors, and morphology, etc.) in order to determine thetype of remedial therapy that is needed (e.g., bradycardia pacing,anti-tachycardia pacing, cardioversion shocks or defibrillation shocks,collectively referred to as “tiered therapy”).

Microcontroller 60 utilizes arrhythmia detector 75 and morphologydetector 77 to recognize and classify arrhythmia so that appropriatetherapy can be delivered. The morphology detector 77 may also be used todetect signal morphologies that are useful for detecting T-wavealternans, in accordance with embodiments of the present inventiondescribed below. The arrhythmia detector 75 and morphology detector 77can be implemented within the microcontroller 60, as shown in FIG. 2.Thus, these elements can be implemented by software, firmware, orcombinations thereof. It is also possible that all, or portions, ofthese detectors can be implemented using hardware.

Cardiac signals are also applied to the inputs of an analog-to-digital(AID) data acquisition system 90. Data acquisition system 90 isconfigured to acquire intracardiac electrogram signals, convert the rawanalog data into a digital signal, and store the digital signals forlater processing and/or telemetric transmission to an external device102. Data acquisition system 90 is coupled to right atrial lead 20,coronary sinus lead 24, and right ventricular lead 30 through switch 74to sample cardiac signals across any pair of desired electrodes.

Data acquisition system 90 can be coupled to microcontroller 60, orother detection circuitry, for detecting an evoked response from heart12 in response to an applied stimulus, thereby aiding in the detectionof “capture.” Capture occurs when an electrical stimulus applied to theheart is of sufficient energy to depolarize the cardiac tissue, therebycausing the heart muscle to contract. Microcontroller 60 detects adepolarization signal during a window following a stimulation pulse, thepresence of which indicates that capture has occurred. Microcontroller60 enables capture detection by triggering ventricular pulse generator72 to generate a stimulation pulse, starting a capture detection windowusing timing control circuitry 79 within microcontroller 60, andenabling data acquisition system 90 via a control signal 92 to samplethe cardiac signal that falls in the capture detection window and, basedon the amplitude, determines if capture has occurred. Additionally,microcontroller 60 can detect cardiac events, such as prematurecontractions of ventricles, and the like.

The implementation of capture detection circuitry and algorithms arewell known. See for example, U.S. Pat. No. 4,729,376 (Decote, Jr.); U.S.Pat. No. 4,708,142 (Decote, Jr.); U.S. Pat. No. 4,686,988 (Sholder);U.S. Pat. No. 4,969,467 (Callaghan et, al.); and U.S. Pat. No. 5,350,410(Mann et. al.), which patents are hereby incorporated herein byreference. The type of capture detection system used is not critical tothe present invention.

Microcontroller 60 is further coupled to a memory 94 by a suitabledata/address bus 96, wherein the programmable operating parameters usedby microcontroller 60 are stored and modified, as required, in order tocustomize the operation of ICD 10 to suit the needs of a particularpatient. Such operating parameters define, for example, pacing pulseamplitude, pulse duration, electrode polarity, rate, sensitivity,automatic features, arrhythmia detection criteria, and the amplitude,waveshape and vector of each shocking pulse to be delivered to heart 12within each respective tier of therapy.

The operating parameters of ICD 10 may be non-invasively programmed intomemory 94 through telemetry circuit 100 in telemetric communication withexternal device 102, such as a programmer, transtelephonic transceiver,or a diagnostic system analyzer. Telemetry circuit 100 is activated bymicrocontroller 60 by a control signal 106. Telemetry circuit 100advantageously allows intracardiac electrograms and status informationrelating to the operation of ICD 10 (as contained in microcontroller 60or memory 94) to be sent to external device 102 through establishedcommunication link 104.

For examples of such devices, see U.S. Pat. No. 4,809,697, entitled“Interactive Programming and Diagnostic System for use with ImplantablePacemaker” (Causey, Ill et al.); U.S. Pat. No. 4,944,299, entitled “HighSpeed Digital Telemetry System for Implantable Device” (Silvian); andU.S. Pat. No. 6,275,734, entitled “Efficient Generation of SensingSignals in an Implantable Medical Device such as a Pacemaker or ICD”(McClure et at), which patents are hereby incorporated herein byreference.

ICD 10 further includes a physiologic sensor 108 that can be used todetect changes in cardiac performance or changes in the physiologicalcondition of the heart. Accordingly, microcontroller 60 can respond byadjusting the various pacing parameters (such as rate, AV Delay, RV-LVDelay, V-V Delay, etc.). Microcontroller 60 controls adjustments ofpacing parameters by, for example, controlling the stimulation pulsesgenerated by the atrial and ventricular pulse generators 70 and 72.While shown as being included within ICD 10, it is to be understood thatphysiologic sensor 108 may also be external to ICD 10, yet still beimplanted within or carried by the patient. More specifically, sensor108 can be located inside ICD 10, on the surface of ICD 10, in a headerof ICD 10, or on a lead (which can be placed inside or outside thebloodstream).

Also shown in FIG, 2 is an activity sensor 116. The activity sensor 116(e.g., an accelerometer) can be used to determine the activity of thepatient. Such information can be used for rate responsive pacing, or, inaccordance with embodiments of the present invention, to determinewhether the patient is sufficiently at rest such that certain baselinemeasurements can be obtained. If the sensor 116 is a multi-dimensionalaccelerometer, then posture information can also be extracted. Thefollowing patents, which are incorporated herein by reference, describeexemplary activity sensors that can be used to detect activity of apatient (some also detect posture): U.S. Pat. No. 6,658,292 to Kroll etal., entitled “Detection of Patient's Position and Activity Status using3D Accelerometer-Based Position Sensor”; U.S. Pat. No, 6,466,821 toKroll et al., entitled “Orientation of Patient's Position Sensor usingExternal Field”; and U.S. Pat. No. 6,625,493 to Pianca et al., entitled“AC/DC Multi-Axis Accelerometer for Determining Patient Activity andBody Position.” Simple activity sensors employ a piezoelectric crystalor a cantilever beam having a film of a piezoelectric polymer adhered toa surface of the beam. These are just a few exemplary types of activitysensors 116, which are not meant to be limiting.

The ICD 10 may also include a magnet detection circuitry (not shown),coupled to microcontroller 60. It is the purpose of the magnet detectioncircuitry to detect when a magnet is placed over ICD 10. A clinician mayuse the magnet to perform various test functions of ICD 10 and/or tosignal microcontroller 60 that the external programmer 102 is in placeto receive or transmit data to microcontroller 60 through telemetrycircuit 100.

As further shown in FIG. 2, ICD 10 can have an impedance measuringcircuit 112, which is enabled by microcontroller 60 via a control signal114. The known uses for an impedance measuring circuit 112 include, butare not limited to, lead impedance surveillance during the acute andchronic phases for proper lead positioning or dislodgement; detectingoperable electrodes and automatically switching to an operable pair ifdislodgement occurs; measuring respiration or minute ventilation;measuring thoracic impedance for determining shock thresholds; detectingwhen the device has been implanted; measuring stroke volume; anddetecting the opening of heart valves, etc. The impedance measuringcircuit 112 is advantageously coupled to switch 74 so that any desiredelectrode may be used The impedance measuring circuit 112 is notcritical to the present invention and is shown only for completeness.

In the case where ICD 10 is intended to operate as a cardioverter, paceror defibrillator, it must detect the occurrence of an arrhythmia andautomatically apply an appropriate electrical therapy to the heart aimedat terminating the detected arrhythmia. To this end, microcontroller 60further controls a shocking circuit 16 by way of a control signal 18.The shocking circuit 16 generates shocking pulses of low (up to about0.5 Joules), moderate (about 0.5-10 Joules), or high energy (about 11 to40 Joules), as controlled by microcontroller 60. Such shocking pulsesare applied to the patient's heart 12 through at least two shockingelectrodes (e.g., selected from left atrial coil electrode 28, RV coilelectrode 36, and SVC coil electrode 38). As noted above, housing 40 mayact as an active electrode in combination with RV electrode 36, or aspart of a split electrical vector using SVC coil electrode 38 or leftatrial coil electrode 28 (i.e., using the RV electrode as a commonelectrode).

Cardioversion shocks are generally considered to be of low to moderateenergy level (so as to minimize pain felt by the patient), and/orsynchronized with an R-wave and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (i.e., corresponding to thresholds in the range of about5-40 Joules), delivered asynchronously (since R-waves may be toodisorganized to be recognize), and pertaining exclusively to thetreatment of fibrillation. Accordingly, microcontroller 60 is capable ofcontrolling the synchronous or asynchronous delivery of the shockingpulses.

ICD 10 additionally includes a battery 110, which provides operatingpower to a load that includes all of the circuits shown in FIG. 2.

TWA Detection

Referring back to FIG. 2, in accordance with embodiments of the presentinvention, microcontroller 60 includes a T-wave alternan (TWA) detector202, which as described in more detail below, can detect the presence ofT-wave alternans. The TWA detector 202 can be implemented within themicrocontroller 60, as shown in FIG. 2. Thus, TWA detector 202 can beimplemented by software, firmware, or combinations thereof. It is alsopossible that all, or portions, of TWA detector 202 can be implementedusing hardware. Further, it is possible that all, or portions, of TWAdetector 202 be implemented external to the microcontroller 60.

In an embodiment, TWA detector 202 triggers data acquisition circuit 90and timing control circuit 79 to record IEGM signal informationfollowing intrinsic, induced or simulated premature contractions of theventricles. TWA detector 202 can measure T-wave metrics, such as T-waveamplitude, T-wave amplitude, T-wave width, T-wave slope, T-wave area,T-wave morphology, QT interval, evoked QT interval, etc. in the IEGMsignal generated by the sensing circuits of the data acquisition system90. TWA detector 202 can also trigger implantable device 10 to respondappropriately when T-wave alternans are detected, as will be explainedin more detail below. Additionally, in conjunction with a telemetrycircuit 100, TWA detector 202 can be configured to deliver statusinformation, relating to the patient's T-wave alternans, to an externaldevice 102 through an established communication link 104. TWA detector202 may also trigger a patient or physician alert in response todetecting T-wave alternans. For example, a patient alert 118, whichproduces a vibratory or auditory alert, may be triggered by the TWAdetector 202.

T-wave alternans have been demonstrated in many studies to be strongpredictor of mortality, independent of left ventricular ejectionfraction (LVEF). It has been generally believed that an elevatedconstant heart rate is a requirement for the detection of T-wavealternans. However, a recent work published by Bullinga et al., entitled“Resonant Pacing Improves T-wave Alternans Testing in Patients withDilated Cardiomyopathy” (Heart Rhythm v1:S129, 2004) revealed a morerobust detection with “resonant pacing” scheme. In this technique, TWAwith higher amplitudes were detected by pacing at a relatively shorterinterval periodically once every fourth cycle during a moderately fastand constant pacing routine. However, Bullinga's scheme still requiresthat a patient be paced at an elevated heart rate, which for variousreasons is not always desirable. Additionally, in Bullinga's techniquethe heart is perturbed continuously for a certain period in order to geta response, and then the response is scaled and translated intomyocardial stability.

It is believed that T-wave amplitudes will also be elevated followingintrinsic premature contractions of the ventricles when the myocardiumis electrically unstable, and thus, that T-wave alternans can bedetected by monitoring T-waves in a predetermined number of beats (e.g.,2 to 10 beats) that follow intrinsic premature contractions of theventricles. While these embodiments of the present invention can be usedeven when there is not a moderately fast and/or constant pacing routine,they can also be used when intrinsic premature ventricular contractionsoccur during a pacing routing (at normal or moderately fast rates).Additionally, the techniques of the present invention care also be usedwhen a patient's intrinsic heart rate is not elevated, as well as when apatient's intrinsic heart rate is elevated.

As mentioned above, T-wave alternans are a known predictor of arrhythmicevents such as tachyarrhythmias. Accordingly, in an embodiment, apatient is alerted (e.g., using alert 118) when T-wave alternans aredetected. Such an alert could be a vibratory or auditory alert thatoriginates from within the implantable device 10. Alternatively, theimplantable device 10 may wirelessly transmit an alert to an externaldevice that produces a visual or auditory alert that a patient can seeor hear. The alert may inform that patient that he should rest, or ifthe patient is operating some type of dangerous machinery (e.g., a car),that the patient should stop what they are doing. By alerting thepatient to rest, it is possible the a tachyarrhythmia may be avoided, orif it does occur, the patient will be less dangerous to themselves andothers if the patient is resting when the tachyarrhythmias occurs (asopposed, e.g., to driving a car).

Additionally or alternatively, the patient can be instructed to takemedication when alerted. In still another embodiment, a physician orother person (e.g., a caregiver, guardian or relative of the patient) isalerted whenever the presence of T-wave alternans is detected.

In further embodiments, therapy can be triggered in response todetecting the presence of T-wave alternans. One type of therapy would befor an implanted device (e.g., device 10) to stimulate the patient'svagus nerve, in an attempt to prevent an arrhythmia from occurring. Inanother embodiment, the implanted device, if appropriately equipped, candeliver appropriate drug therapy. In still another embodiment, theimplanted device, if appropriately equipped, can deliver appropriatepacing therapy. In still another embodiment, the implantable device, ifcable of delivering shock therapy, can begin to charge its capacitors incase the patient goes into ventricular fibrillation and needs shocktherapy. These are just a few examples of the types of responses thatcan be performed upon detection of T-wave alternans. One of ordinaryskill in the art would understand from the above description that otherresponse are also possible, while still being within the spirit andscope of the present invention.

An advantage of the embodiments of the present invention is that theseembodiments can be performed by an implantable device (such as animplantable monitoring device) that does not include stimulationcapabilities. This, however, does not mean that these embodiments cannot be implemented by an implantable device that does provide forstimulation capabilities, as can be appreciated from the abovediscussion. Another advantage of these embodiments is that they enableT-wave alternans to be monitored for without requiring elevation of apatient's heart rate through exercise or overdrive pacing. In otherwords, with embodiments of the present invention the state of a heartcan be assessed in its sort of native and un-paced state. This isespecially advantageous with patients that are for whatever reasonphysically incapacitated or limited such that elevating their heart ratewould be difficult and/or dangerous. Nevertheless, as stated above,these embodiments can also be used if a patient's heart happens to beelevated.

One response can be to store information related to the metrics ofT-waves for later retrieval and/or transmission to a physician or otherclinician. Another response involves triggering a patient or physicianalert that warns of an impending arrhythmia, thereby allowing thepatient to respond appropriately. Such an alert could be, e.g., avibratory or auditory alert that originates from within an implantabledevice. Alternatively, an implantable device may wirelessly transmit analert to an external device that produces a visual or auditory alertthat a patient can see or hear. The alert may inform that patient thathe should rest, or if the patient is operating some type of dangerousmachinery (e.g., a car), that the patient should stop what they aredoing. Additionally or alternatively, the patient can be instructed totake medication when alerted. In further embodiments, a preventivetherapy can be triggered in response to assessing a risk of an impendingarrhythmia. One type of therapy would be for an implanted device (e.g.,device 10) to stimulate the vagal nerve, in an attempt to slow down theheart rate. Another response would be to deliver an appropriateanti-arrhythmia pacing therapy. In another embodiment, the implanteddevice, if appropriately equipped, can deliver an appropriate drugtherapy. One of ordinary skill in the art would appreciate from theabove description that other types of therapies can be triggered. Theseare just a few examples of the types of responses that can be performedupon assessing a risk of an impending arrhythmia. One of ordinary skillin the art would understand from the above description that otherresponses are also possible, while still being within the spirit andscope of the present invention.

In further embodiments, changes in magnitudes of alternation are trackedthereby track changes in myocardial electrical stability. This caninclude recognizing increases in magnitudes of alternations as beingindicative of increased electrical instability of the myocardium, andrecognizing decreases in magnitudes of alternations as being indicativeof increased electrical stability of the myocardium.

In accordance with one embodiment of the invention an approach toprospectively predict the complexity of arrhythmias based on beat bybeat alterations before the actual arrhythmia onset is provided. Thismethod provides an early prediction of an arrhythmia and allows foroptimizing antiarrhythmia therapy. In this embodiment, the method isused in implantable devices to predict the complexity of coming VT/VFbased on beat by beat alterations before the actual onset of VT/VF. Themethod extracts EGM features and tracks beat by beat alterations. Thesefeatures may include the amplitude, duration, slope, area under thecurve of QRS complex and T wave portion, as well as conduction velocity.Table 1. provides some features that can be extracted from ventricularIEGM. Based on the degree of alterations, the method predicts thecomplexity of VT/VF and selects optimal therapy. For example, the devicecan be programmed to reduce the number of ATP attempts when the methodpredicts high complexity. Alternatively, ATP can be skipped altogetherand the device can move tachyarrhythmia therapy directly tocardioversion shocks.

TABLE 1 No. Feature Description 1 Heart Rate Calculated based on Beat toBeat RR interval 2 Rpeak2peak QRS peak to peak Amplitude (Amplitude fromC to F) 3 Rtime1 = QRStime1 Timing between maximum slope to negative QRSPeak (B to F) 4 Rtime2 = QRStime2 Timing between maximum slope tominimum slope in QRS (B to D) 5 Rtime3 = QRStime3 Timing between 2 ZeroCrossing in QRS (A to E) 6 Tpeak2peak T wave peak to peak Amplitude(Amplitude from I to G) 7 Tpeaktime Timing between QRS and Tpeak (C toI) 8 Tpeaktime_Bazett Tpeaktime corrected by Bazett equation:Tpeaktime/sqrt (RR-interval) 9 Tpeaktime_Hodges Tpeaktime corrected byHodges equation: Tpeaktime + (1.75*(current beat HR-60)) 10 TmaxslopeMaximum Slope in T wave (Value at H) 11 Tmaxslope_time Timing betweenQRS and max T slope (C to H) 12 Tminslope Minimum Slope in T wave (Valueat J) 13 Tminslope_time Timing between QRS and min T slope (C to J) 14Tarea Area under T wave 15 Ttime1 T wave duration calculated bycorrected Start and End of T wave 16 Ttime2 Timing between max and minslope in T wave (H to J) 17 Ttime3 Timing between 2 Zero Crossing in Twave (H to K)

In some embodiments, it is desirable to use a heart rate dependent Twave correction which can be used in T wave alternans detection in EGMrecordings. A general form of the equation is:

$\begin{matrix}{T = \frac{A}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{B} \right)^{k}}} & {{Eq}.\mspace{14mu} 1}\end{matrix}$

For example, the equations below identify the start and end of T wavesaccurately for heart rates ranging from 50 to 160 bpm as provided inFIG. 3 where T wave start and end time from R wave for heart rate rangedfrom 50 to 160 bpm.

$\begin{matrix}{T_{start} = \frac{160}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{60} \right)^{0.5}}} & {{Eq}.\mspace{14mu} 2} \\{T_{end} = \frac{480}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{70} \right)^{0.7}}} & {{Eq}.\mspace{14mu} 3}\end{matrix}$

where T_(start) & T_(end) are the start and end time from the peak ofthe QRS.

Another embodiment of the invention involves a method used inimplantable devices to identify vulnerability and risk of arrhythmias.Once a PVC is detected, several features are calculated and saved in thedevice. These features include averaged heart rate before the PVC,premature coupling interval of the PVC, averaged T wave duration beforethe PVC, and morphological characteristics (amplitude, large negativepeak, etc.) of the PVC. The implantable device also registers lethal PVCcharacteristics if VT/VF (both sustained and non-sustained) is triggeredby a PVC. The characteristics of newly detected PVCs will be compared toan existing template to determine the likelihood of arrhythmiainitiation. If the chance of arrhythmia initiation is high, the devicecan respond correspondingly to reduce the chance of arrhythmiainitiation through pacing interruption and may start to prepareantiarrhythmia therapy before an arrhythmia happens such as by charginghigh voltage capacitors.

In another embodiment of the invention a time domain method is used topredict risks of spontaneous VT/VF by tracking beat to beat alterationsin extracted EGM features. As an example, Table 1 lists the extractedfeatures from a ventricular EGM recording. Beat to beat alterations inamplitude and pattern from some or all of these extracted features willbe fed into a mathematical model to predict risks of arrhythmias.

This invention further consists of a new method to monitor thetransition pattern of beat by beat variation of any electrical andmechanical characteristics. These characteristics include but are notlimited to intervals (R.-R interval, Q-T interval, etc), EGM amplitudes(QRS amplitude, T wave amplitude, etc), and their analogies derived fromintracardiac impedance. For any single or combined characteristic, thebeat by beat variation will be calculated by subtracting the valueassociated with the current beat by the value associated with itsprevious beat.

Further, the transition pattern of beat to beat variations in IEGM canbe calculated by the percentage of reversal point (PRP) within a certaintime window based on Eq. 3. PRP value will be used as a risk indicatorof arrhythmias.

$\begin{matrix}{{PRP} = \frac{{{number}\mspace{14mu} {of}\mspace{14mu} {reversal}\mspace{14mu} {point}\mspace{14mu} {within}\mspace{14mu} {the}\mspace{14mu} {window}} - 2}{\begin{matrix}{{total}\mspace{14mu} {number}\mspace{14mu} {of}{\mspace{11mu} \;}{beats}\mspace{14mu} {from}} \\{\; {{{the}\mspace{14mu} 1\; {st}\mspace{14mu} {to}\mspace{14mu} {the}\mspace{14mu} {last}\mspace{14mu} {reversal}\mspace{14mu} {point}} - 2}}\end{matrix}\mspace{11mu}}} & {{Eq}.\mspace{14mu} 3}\end{matrix}$

FIG. 4 shows two examples with A-B (panel A) and A-B-C (panel B)patterns and their corresponding PRP values. The PRP value can becontinuously calculated in a moving window and generate detection alarmwhen the value fans into each block (e.g. PRP 0.9˜1 for A-B pattern, PRP0.62˜0.72 for A-B-C pattern). In one method, PRP itself can be used totrigger an alarm of vulnerable period to arrhythmias; in another method,PRP will be combined into a multiple factors determining algorithm totrigger an alarm of vulnerable period to arrhythmias.

The PRP calculation can be corrected when a PVC happens within thecalculation window. In one approach. PRP calculation will ignore the PVCbeats and the beats prior and after each PVC beat. In another approach,the value associated with a PVC beat will be replaced by an averagedvalue from the non-PVC beats before PRP calculation.

In another embodiment, the continuous oscillation pattern monitoring canbe used as an indicator of patient health status and diseaseprogression. If the PRP values within a period (e.g. a month) shows asignificant trend of increasing, an alarm indicating heart diseaseprogression or remodeling will be triggered.

In still another embodiment of the invention, a method thatautomatically calculates T wave start and end time based on the heartrate computed from the previous beat is disclosed. This allows one totruncate a portion from the EGM signals at every heart beat and extractcritical features related to T wave instability and correspondinglypredicts the onset of ventricular tachyarrhythmias.

Referring now to FIG. 5, various points in the sensed EGM that may beuseful in practicing the invention are illustrated. In the FIG. 5, thefollowing points represent the time at

-   -   A=Zero Crossing1 for QRS    -   B=Maximum Slope for ORS    -   C=Positive Peak for ORS    -   D=Minimum Slope for ORS    -   E=Zero Crossing2 for ORS    -   F=Negative Peak for ORS    -   G=Negative Peak for T wave    -   H=Zero Crossing1 for T wave, Maximum Slope for T wave (only        here. In actual beat, it may or may not be same)    -   I=Positive Peak for T wave    -   J=Minimum Slope for T wave    -   K=Zero Crossing2 for T wave

FIG. 3 provides an example of using the percentage of reversal point(PRP) to identify A) A-B patterned oscillation and B) A-B-C patternedoscillation. Green circles are the reversal points. PRP is equal to onein A-B patterned oscillation, and ⅔ (=0.67) in A-B-C patternedoscillation.

While the invention has been described by means of specific embodimentsand applications thereof, it is understood that numerous modificationsand variations could be made thereto by those skilled in the art withoutdeparting from the spirit and scope of the invention. It is therefore tobe understood that within the scope of the claims, the invention may bepracticed otherwise than as specifically described herein.

Example embodiments of the methods, systems, and components of thepresent invention have been described herein. As noted elsewhere, theseexample embodiments have been described for illustrative purposes only,and are not limiting. Other embodiments are possible and are covered bythe invention. Such embodiments will be apparent to persons skilled inthe relevant art(s) based on the teachings contained herein.

Thus, the breadth and scope of the present invention should not belimited by any of the above-described exemplary embodiments, but shouldbe defined only in accordance with the claims and their equivalents.

1. A non-transitory computer readable storage medium for a computingdevice having a memory and a microcontroller, the non-transitorycomputer readable storage medium comprising instructions to: record IEGMsignal information prior to intrinsic, induced or simulated prematurecontractions of the ventricles (PVC); detect heart rate over a period oftime prior to the PVC; average heart rate over a period of time prior tothe PVC; determine a premature coupling interval of the PVC; determinean average T wave duration over a period of time prior to the PVC,wherein the period of time is an R-R interval and wherein the heart rateis between about 50 bpm to about 160 bpm; calculate a T-wave start timeusing the formula:${T_{start} = \frac{160}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{60} \right)^{0.5}}};$calculate a T-wave end time using the formula:${T_{end} = \frac{480}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{70} \right)^{0.7}}},$where T_(start) and T_(end) are the start and end time from the peak ofa QRS; determine the T-wave duration as the time between T_(start) andT_(end); determine a morphology of the PVC; compare the prematurecoupling interval of the PVC, average T wave duration over a period oftime prior to the PVC, premature coupling interval of the PVC average Twave duration over a period of time prior to the PVC, and morphology ofthe PVC to a template; and determine the likelihood of arrhythmiainitiation based on the comparing step.
 2. The non-transitory computerreadable storage medium of claim 1, wherein the instructions direct themicrocontroller to trigger one or more responses based on a likelihoodof arrhythmia initiation.
 3. The non-transitory computer readablestorage medium of claim 2, wherein the response is preparingantiarrhythmia therapy before the occurrence of an arrhythmia.
 4. Thenon-transitory computer readable storage medium of claim 2, wherein theresponse is charging a high voltage capacitor.
 5. The non-transitorycomputer readable storage medium of claim 1, wherein the instructionsdirect the microcontroller to: record ventricular EGM signal informationfollowing intrinsic, induced or simulate premature contractions of theventricles (PVC); extract features from the ventricular EGM recording;track beat to beat alterations in the extracted features of the EGMsignal; and predict a risk of spontaneous VT/VF based on the beat tobeat alterations in IEGM signal information.
 6. The non-transitorycomputer readable storage medium of claim 5, wherein the EGM featurescomprise at least one of the following: a heart rate, calculated basedon beat to beat RR interval; an R peak to peak, calculated based on aQRS peak to peak amplitude; Rtime1=QRStime1, calculated based on timingbetween maximum slope to negative QRS peak; Rtime2=QRStime2, calculatedbased on timing between maximum slope to minimum slope in QRS;Rtime3=QRStime3, calculated based on timing between 2 Zero Crossing inQRS; Tpeak2peak, calculated based on T wave peak to peak Amplitude;Tpeaktime, calculated based on timing between QRS and Tpeak;Tpeaktime_Bazett calculated based on Tpeaktime corrected by Bazettequation:Tpeaktime/sqrt (RR-interval); Tpeaktime_Hodges, calculated based onTpeaktime corrected by Hodges equation:Tpeaktime+(1.75*(current beat HR-60)); Tmaxslope, calculated based onMaximum Slope in T wave; Tmaxslope_time, calculated based on timingbetween ORS and max T slope Tminslope, calculated based on minimum slopein T wave; Tminslope_time, calculated based on Ttming between QRS andmin T slope; Tarea, calculated based on area under T wave; Ttime1,calculated based on T wave duration calculated by corrected Start andEnd of T wave; Ttime2, calculated based on timing between max and minslope in T wave; and Ttime3, calculated based on timing between 2 ZeroCrossing in T wave.
 7. The non-transitory computer readable storagemedium of claim 1, wherein the instructions direct the microcontrollerto: record IEGM signal information; determine a transitions pattern ofbeat to beat variations in IEGM by calculating the percentage ofreversal point (PRP) within a certain time window using the formula:${{PRP} = \frac{{{number}\mspace{14mu} {of}\mspace{14mu} {reversal}\mspace{14mu} {point}\mspace{14mu} {within}\mspace{14mu} {the}\mspace{14mu} {window}} - 2}{\begin{matrix}{{total}\mspace{14mu} {number}\mspace{14mu} {of}{\mspace{11mu} \;}{beats}\mspace{14mu} {from}} \\{\; {{{the}\mspace{14mu} 1\; {st}\mspace{14mu} {to}\mspace{14mu} {the}\mspace{14mu} {last}\mspace{14mu} {reversal}\mspace{14mu} {point}} - 2}}\end{matrix}\mspace{11mu}}};$ and use the PRP value to determine a riskof arrhythmia.
 8. The non-transitory computer readable storage medium ofclaim 7, wherein the instructions direct the microcontroller to:continuously calculate the PRP value in a moving time window; andgenerate a detection alarm when the PRP value indicates a risk ofarrhythmia.
 9. The non-transitory computer readable storage medium ofclaim 7, wherein the instructions direct the microcontroller to correctthe PRP value when a PVC beat happens within the time window.
 10. Thenon-transitory computer readable storage medium of claim 9, wherein theinstructions direct the microcontroller to ignore a PVC beat within thetime window and the beat prior to and after the PVC beat in calculatingof the PRP value.
 11. The non-transitory computer readable storagemedium of claim 9, wherein the instructions direct the microcontrollerto replace the PVC beat within the time window with an average value ofbeats from the non-PVC beats before the PVC beat.
 12. The non-transitorycomputer readable storage medium of claim 7, wherein the instructionsdirect the microcontroller to monitor PRP values over a period of timeand determine the progression of heart disease or remodeling of theheart based on said monitoring of the PRP values.
 13. A non-transitorycomputer readable storage medium for a computing device having a memoryand a microcontroller, the non-transitory computer readable storagemedium comprising instructions to: detect heart rate over a period oftime, wherein the period of time is an R-R interval and wherein theheart rate is between about 50 bpm to about 160 bpm; calculate a T-wavestart time using the formula:${T_{start} = \frac{160}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{60} \right)^{0.5}}};$calculate a T-wave end time using the formula:${T_{end} = \frac{480}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{70} \right)^{0.7}}},$where T_(start) and T_(end) are the start and end time from the peak ofa QRS; determine the T-wave duration as the time between T_(start) andT_(end); and record the T-wave duration,
 14. A non-transitory computerreadable storage medium for a computing device having a memory and amicrocontroller, the non-transitory computer readable storage mediumcomprising instructions to: record IEGM signal information followingintrinsic, induced or simulated premature contractions of the ventricles(PVC); detect heart rate over a period of time following the PVC,wherein the period of time is an R-R interval and wherein the heart rateis between about 50 bpm to about 160 bpm; calculate a T-wave start timeusing the formula:${T_{start} = \frac{160}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{60} \right)^{0.5}}};$calculate a T-wave end time using the formula:${T_{end} = \frac{480}{\left( \frac{{Heart}\mspace{14mu} {Rate}}{70} \right)^{0.7}}},$where T_(start) and T_(end) are the start and end time from the peak ofa QRS; determine the T-wave duration as the time between T_(start) andT_(end); record the T-wave duration; extract EGM features; track beat bybeat alterations of the EGM features; and predict the complexity of apredicted arrhythmia based on beat by beat alternations before an actualarrhythmia,
 15. The non-transitory computer readable storage medium ofclaim 14, wherein the EGM features comprise: a heart rate, calculatedbased on beat to beat RR interval; an R peak to peak, calculated basedon a QRS peak to peak amplitude; Rtime1=QRStime1, calculated based ontiming between maximum slope to negative QRS peak; Rtime2=QRStime2,calculated based on timing between maximum slope to minimum slope inQRS; Rtime3=QRStime3, calculated based on timing between 2 Zero Crossingin QRS; Tpeak2peak, calculated based on T wave peak to peak Amplitude;Tpeaktime, calculated based on timing between QRS and Tpeak;Tpeaktime_Bazett, calculated based on Tpeaktime corrected by Bazettequation:Tpeaktime/sqrt (RR-interval); Tpeaktime_Hodges, calculated based onTpeaktime corrected by Hodges equation:Tpeaktime+(1.75*(current beat HR-60)); Tmaxslope, calculated based onMaximum Slope in T wave; Tmaxslope_time, calculated based on timingbetween QRS and max T slope Tminslope, calculated based on minimum slopein T wave; Tminslope_time, calculated based on Ttming between QRS andmin T slope; Tarea, calculated based on area under T wave; Ttime1,calculated based on T wave duration calculated by corrected Start andEnd of T wave: Ttime2, calculated based on timing between max and minslope in T wave; and Ttime3, calculated based on timing between 2 ZeroCrossing in T wave.
 16. The non-transitory computer readable storagemedium of claim 14, wherein the instructions direct the microcontrollerto trigger one or more responses based the complexity of the predictedarrhythmia.
 17. The non-transitory computer readable storage medium ofclaim 16, wherein the response is stimulating a vagal nerve.
 18. Thenon-transitory computer readable storage medium of claim 14, wherein theinstructions direct the microcontroller to track beat by beatalterations of the EGM features by subtracting the value of an EGMfeature of a current beat by a value associated with a previous beat.